Abstract

Backround

Neuroprotective strategies after cardiopulmonary resuscitation are currently the focus of experimental and clinical research. Levosimendan has been proposed as a promising drug candidate because of its cardioprotective properties, improved haemodynamic effects in vivo and reduced traumatic brain injury in vitro. The effects of levosimendan on brain metabolism during and after ischaemia/hypoxia are unknown.

Methods

Transient cerebral ischaemia/hypoxia was induced in 30 male Wistar rats by bilateral common carotid artery clamping for 15 min and concomitant ventilation with 6% O2 during general anaesthesia with urethane. After 10 min of global ischaemia/hypoxia, the rats were treated with an i.v. bolus of 24 μg kg-1 levosimendan followed by a continuous infusion of 0.2 μg kg-1 min-1. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glutamate were monitored by microdialysis. In addition, the effects on global haemodynamics, cerebral perfusion and autoregulation, oedema and expression of proinflammatory genes in the neocortex were assessed.

Conclusion

Although levosimendan has neuroprotective actions in vitro and on the spinal cord in vivo and has been shown to cross the blood–brain barrier, the present results showed that levosimendan did not reduce the initial neuronal injury after transient ischaemia/hypoxia.

Guide for the care and use of laboratory animals: Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council. 8th edition. Washington, DC: National Academy Press; 2011.